tbuckley/cabot-search huggingface dataset:
European Epidemiology of Pleural Mesothelioma—Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database
Authors: Isabelle Opitz, Andrea Bille, Urania Dafni, Kristiaan Nackaerts, Luca Ampollini, Marc de Perrot, Luka Brcic, Ernest Nadal, Konstantinos Syrigos, Steven G. Gray, Joachim Aerts, Alessandra Curioni-Fontecedro, Jan H. Rüschoff, Kim Monkhorst, Birgit Weynand, Enrico Maria Silini, Fatemeh Bavaghar-Zaeimi, Marko Jakopovic, Roger Llatjos, Sotirios Tsimpoukis, Stephen P. Finn, Jan von der Thüsen, Nesa Marti, Georgia Dimopoulou, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Pierre-Emmanuel Falcoz, Alessandro Brunelli, Paul Baas, Rolf Stahel, Anita Hiltbrunner, Rosita Kammler, Nesa Marti, Barbara Ruepp, Urania Dafni, Zoi Tsourti, Panagiota Zygoura, Katerina Vervita, Georgia Dimopoulou, Charitini Andriakopoulou, Androniki Stavrou, Jan H. Rüschoff, Martina Haberecker, Susanne Dettwiler, Fabiola Prutek, Christiane Mittmann, Isabelle Opitz, Bart Vrugt, Martina Friess, Alessandra Matter, Chloé Spichiger-Häusermann, Michaela B. Kirschner, Emanuela Felley-Bosco, Paul Baas, Kim Monkhorst, Kristiaan Nackaerts, Eric Verbeken, Birgit Weynand, Philippe Nafteux, Johnny Moons, Liesbet Peeters, Luca Ampollini, Marcello Tiseo, Enrico Maria Silini, Letizia Gnetti, Paolo Carbognani, Marc de Perrot, Fatemeh Bavaghar-Zaeimi, Luka Brcic, Miroslav Samarzija, Sven Seiwerth, Marko Jakopovic, Ernest Nadal, Felipe Cardenal, Roger Llatjos, Susana Lorente, Konstantinos Syrigos, Ioannis Vamvakaris, Sotirios Tsimpoukis, Paraskevi Boura, Steven G. Gray, Stephen P. Finn, Mutaz Mohammed Nur, Anne-Marie Baird, Martin P. Barr, Sinead Cuffe, Kathy Gately, Joachim Aerts, Jan von der Thüsen, Andrea Bille, Stefano Passani, Alessandro Brunelli
Journal: Journal of Thoracic Oncology (2023)
Multi-target landmark detection with incomplete images via reinforcement learning and shape prior embedding
Authors: Kaiwen Wan, Lei Li, Dengqiang Jia, Shangqi Gao, Wei Qian, Yingzhi Wu, Huandong Lin, Xiongzheng Mu, Xin Gao, Sijia Wang, Fuping Wu, Xiahai Zhuang
Journal: Medical Image Analysis (2023)
Unveiling the benefits of multitasking in disentangled representation formation
Authors: Jenelle Feather, SueYeon Chung
Journal: Trends in Cognitive Sciences (2023)

Johnston and Fusi recently investigated the emergence of disentangled representations when a neural network was trained to perform multiple simultaneous tasks. Such experiments explore the benefits of flexible representations and add to a growing field of research investigating the representational geometry of artificial and biological neural networks.
A cost-utility analysis of two Clostridioides difficile infection guideline treatment pathways
Authors: Nicholas Swart, Araadhna M. Sinha, Anthony Bentley, Helen Smethurst, Gordon Spencer, Sophia Ceder, Mark H. Wilcox
Journal: Clinical Microbiology and Infection (2023)

Treatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service.A decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature.The ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy.Compared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service.
Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin
Authors: Julio Rosenstock, Stephen C Bain, Amoolya Gowda, Esteban Jódar, Bo Liang, Ildiko Lingvay, Tomoyuki Nishida, Roberto Trevisan, Ofri Mosenzon
Journal: New England Journal of Medicine (2023)

Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded.Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, -1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, -1.35 percentage points]); the estimated between-group difference (-0.19 percentage points; 95% confidence interval [CI], -0.36 to -0.03) confirmed the noninferiority (P<0.001) and superiority (P = 0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups.Glycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100. (Funded by Novo Nordisk; ONWARDS 1 ClinicalTrials.gov number, NCT04460885.).
Agreement and reliability of remote assessment of actinic keratosis: a proof-of-concept study using smartphone photographs
Authors: Vinzent Kevin Ortner, John R Zibert, Ionela  Manole, Alejandro Castillo Mondragón, Anders Daniel Andersen, Merete Haedersdal
Journal: British Journal of Dermatology (2023)

Despite a rapidly growing interest in use of teledermatology, validation of conventional in-clinic scoring systems for remote assessment of actinic keratosis (AK) fails to keep pace. In this paper, we describe the level of agreement between in-clinic and remote assessments of AK using two different conventional scoring systems. The results of our proof-of-concept study encourage the use of patient-obtained smartphone photographs for standardized remote assessment but highlight the need for adjustments to the currently available scoring systems to improve their reliability. The results of this study may pave the road for the implementation of remote assessments of AK in a clinical management plan.
Single genomic enhancers drive experience-dependent GABAergic plasticity to maintain sensory processing in the adult cortex
Authors: Ori Roethler, Eran Zohar, Katayun Cohen-Kashi Malina, Lidor Bitan, Harrison Wren Gabel, Ivo Spiegel
Journal: Neuron (2023)

Experience-dependent plasticity of synapses modulates information processing in neural circuits and is essential for cognitive functions. The genome, via non-coding enhancers, was proposed to control information processing and circuit plasticity by regulating experience-induced transcription of genes that modulate specific sets of synapses. To test this idea, we analyze here the cellular and circuit functions of the genomic mechanisms that control the experience-induced transcription of Igf1 (insulin-like growth factor 1) in vasoactive intestinal peptide (VIP) interneurons (INs) in the visual cortex of adult mice. We find that two sensory-induced enhancers selectively and cooperatively drive the activity-induced transcription of Igf1 to thereby promote GABAergic inputs onto VIP INs and to homeostatically control the ratio between excitation and inhibition (E/I ratio)-in turn, this restricts neural activity in VIP INs and principal excitatory neurons and maintains spatial frequency tuning. Thus, enhancer-mediated activity-induced transcription maintains sensory processing in the adult cortex via homeostatic modulation of E/I ratio.
Machine learning to predict poor school performance in paediatric survivors of intensive care: a population-based cohort study
Authors: Patricia Gilholm, Kristen Gibbons, Sarah Brüningk, Juliane Klatt, Rhema Vaithianathan, Debbie Long, Johnny Millar, Wojtek Tomaszewski, Luregn J. Schlapbach, Anusha Ganeshalingam, Claire Sherring, Simon Erickson, Samantha Barr, Sainath Raman, Debbie Long, Luregn Schlapbach, Kristen Gibbons, Shane George, Puneet Singh, Vicky Smith, Warwick Butt, Carmel Delzoppo, Johnny Millar, Ben Gelbart, Felix Oberender, Subodh Ganu, Georgia Letton, Marino Festa, Gail Harper
Journal: Intensive Care Medicine (2023)

Whilst survival in paediatric critical care has improved, clinicians lack tools capable of predicting long-term outcomes. We developed a machine learning model to predict poor school outcomes in children surviving intensive care unit (ICU).
Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease
Authors: Dhruv S. Kazi
Journal: JAMA (2023)

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<i>Pyemotes ventricosus</i> Dermatitis
Authors: Jean-Michel Berenger, Phillippe Parola
Journal: New England Journal of Medicine (2023)

A 30-year-old man and woman presented with itchy skin lesions. Erythematous macules from which serpiginous tracts emanated looked like comets. Beetle infestation was identified in the couple’s furniture. A diagnosis was made.
Sharing Pathogen Genomic Sequence Data — Toward Effective Pandemic Prevention, Preparedness, and Response
Authors: Sam Halabi, Richard Wilder, Lawrence O. Gostin, Maria Luisa Hurtado
Journal: New England Journal of Medicine (2023)

Interview with Sam Halabi on facilitating sharing and aggregation of pathogen genomic sequence data for public health objectives. (10:09)Download Despite the importance of information about pathogens' genomic sequences, there is no global system for sharing such data. Various repositories where data are shared operate on different principles.
Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology
Authors: Jihoon Lee, Ki Woon Sung, Eun-Jin Bae, Dabin Yoon, Dasarang Kim, Jin Saem Lee, Da-Ha Park, Daniel Youngjae Park, Su Ran Mun, Soon Chul Kwon, Hye Yeon Kim, Joo-Ok Min, Seung-Jae Lee, Young Ho Suh, Yong Tae Kwon
Journal: Molecular Neurodegeneration (2023)

There are currently no disease-modifying therapeutics for Parkinson's disease (PD). Although extensive efforts were undertaken to develop therapeutic approaches to delay the symptoms of PD, untreated α-synuclein (α-syn) aggregates cause cellular toxicity and stimulate further disease progression. PROTAC (Proteolysis-Targeting Chimera) has drawn attention as a therapeutic modality to target α-syn. However, no PROTACs have yet shown to selectively degrade α-syn aggregates mainly owing to the limited capacity of the proteasome to degrade aggregates, necessitating the development of novel approaches to fundamentally eliminate α-syn aggregates.We employed AUTOTAC (Autophagy-Targeting Chimera), a macroautophagy-based targeted protein degradation (TPD) platform developed in our earlier studies. A series of AUTOTAC chemicals was synthesized as chimeras that bind both α-syn aggregates and p62/SQSTM1/Sequestosome-1, an autophagic receptor. The efficacy of Autotacs was evaluated to target α-syn aggregates to phagophores and subsequently lysosomes for hydrolysis via p62-dependent macroautophagy. The target engagement was monitored by oligomerization and localization of p62 and autophagic markers. The therapeutic efficacy to rescue PD symptoms was characterized in cultured cells and mice. The PK/PD (pharmacokinetics/pharmacodynamics) profiles were investigated to develop an oral drug for PD.ATC161 induced selective degradation of α-syn aggregates at DC50 of ~ 100 nM. No apparent degradation was observed with monomeric α-syn. ATC161 mediated the targeting of α-syn aggregates to p62 by binding the ZZ domain and accelerating p62 self-polymerization. These p62-cargo complexes were delivered to autophagic membranes for lysosomal degradation. In PD cellular models, ATC161 exhibited therapeutic efficacy to reduce cell-to-cell transmission of α-syn and to rescue cells from the damages in DNA and mitochondria. In PD mice established by injecting α-syn preformed fibrils (PFFs) into brain striata via stereotaxic surgery, oral administration of ATC161 at 10 mg/kg induced the degradation of α-syn aggregates and reduced their propagation. ATC161 also mitigated the associated glial inflammatory response and improved muscle strength and locomotive activity.AUTOTAC provides a platform to develop drugs for PD. ATC161, an oral drug with excellent PK/PD profiles, induces selective degradation of α-syn aggregates in vitro and in vivo. We suggest that ATC161 is a disease-modifying drug that degrades the pathogenic cause of PD.
Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH
Authors: Rohit Loomba, Arun J. Sanyal, Kris V. Kowdley, Deepak L. Bhatt, Naim Alkhouri, Juan P. Frias, Pierre Bedossa, Stephen A. Harrison, Donald Lazas, Robert Barish, Mildred D. Gottwald, Shibao Feng, Germaine D. Agollah, Cynthia L. Hartsfield, Hank Mansbach, Maya Margalit, Manal F. Abdelmalek
Journal: New England Journal of Medicine (2023)

Pegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven noncirrhotic NASH are not well established.
Exosome camouflaged coordination-assembled Iridium(III) photosensitizers for apoptosis-autophagy-ferroptosis induced combination therapy against melanoma
Authors: Tao Feng, Zixin Tang, Johannes Karges, Jinchao Shen, Chengzhi Jin, Yu Chen, Yihang Pan, Yulong He, Liangnian Ji, Hui Chao
Journal: Biomaterials (2023)
Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
Authors: Juan P Frias, Srikanth Deenadayalan, Lars Erichsen, Filip K Knop, Ildiko Lingvay, Stanislava Macura, Chantal Mathieu, Sue D Pedersen, Melanie Davies
Journal: The Lancet (2023)
Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study
Authors: Juan P Frias, Stanley Hsia, Sarah Eyde, Rong Liu, Xiaosu Ma, Manige Konig, Christof Kazda, Kieren J Mather, Axel Haupt, Edward Pratt, Deborah Robins
Journal: The Lancet (2023)
5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study
Authors: Jin Yang, Xiaojing Liu, Yajing Cao, Peiru Wang, Haiyan Zhang, Qi Chen, Yutong Yang, Qingyu Zeng, Linglin Zhang, Xiuli Wang
Journal: Journal of the American Academy of Dermatology (2023)
EASL Clinical Practice Guidelines on acute-on-chronic liver failure
Authors: Richard Moreau, Marta Tonon, Aleksander Krag, Paolo Angeli, Marina Berenguer, Annalisa Berzigotti, Javier Fernandez, Claire Francoz, Thierry Gustot, Rajiv Jalan, Maria Papp, Jonel Trebicka
Journal: Journal of Hepatology (2023)
Dual deletion of guanylyl cyclase-A and p38 mitogen-activated protein kinase in podocytes with aldosterone administration causes glomerular intra-capillary thrombi
Authors: Sayaka Sugioka, Hiroyuki Yamada, Akira Ishii, Yukiko Kato, Ryo Yamada, Keita P. Mori, Shoko Ohno, Takaya Handa, Akie Ikushima, Takuya Ishimura, Keisuke Osaki, Takeshi Tokudome, Taiji Matsusaka, Angel R. Nebreda, Motoko Yanagita, Hideki Yokoi
Journal: Kidney International (2023)
Apolipoprotein E in lipid metabolism and neurodegenerative disease
Authors: Linda G. Yang, Zachary M. March, Roxan A. Stephenson, Priyanka S. Narayan
Journal: Trends in Endocrinology and Metabolism (2023)

Dysregulation of lipid metabolism has emerged as a central component of many neurodegenerative diseases. Variants of the lipid transport protein, apolipoprotein E (APOE), modulate risk and resilience in several neurodegenerative diseases including late-onset Alzheimer's disease (LOAD). Allelic variants of the gene, APOE, alter the lipid metabolism of cells and tissues and have been broadly associated with several other cellular and systemic phenotypes. Targeting APOE-associated metabolic pathways may offer opportunities to alter disease-related phenotypes and consequently, attenuate disease risk and impart resilience to multiple neurodegenerative diseases. We review the molecular, cellular, and tissue-level alterations to lipid metabolism that arise from different APOE isoforms. These changes in lipid metabolism could help to elucidate disease mechanisms and tune neurodegenerative disease risk and resilience.
Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes
Authors: Ildiko Lingvay, Marisse Asong, Cyrus Desouza, Pierre Gourdy, Soumitra Kar, André Vianna, Tina Vilsbøll, Siri Vinther, Yiming Mu
Journal: JAMA (2023)

Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes.Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol).Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294).The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes.Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01).Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups.ClinicalTrials.gov Identifier: NCT04795531.
The problem of Mycobacterium abscessus complex: multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission
Authors: Rebekah M. Dedrick, Lawrence Abad, Nathaniel Storey, Ari M. Kaganovsky, Bailey E. Smith, Haley A. Aull, Madison Cristinziano, Anna Morkowska, Saraswathi Murthy, Michael R. Loebinger, Graham F. Hatfull, Giovanni Satta
Journal: Clinical Microbiology and Infection (2023)

Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages.